This proposal is a response to Program Announcement PAR-00-035, Mentored Medical Student Clinical Research Program. The research mentor, Charles B. Hicks, is committed to a career in patient-oriented Human Immunodeficiency virus (HIV) research, a field in which he has been fully involved since coming to Duke in 1994. The proposed program of research will examine possible ways in which some patients with HIV are able to maintain CD4+ lymphocyte levels despite ongoing viral replication. Immune response will be evaluated in three groups of patients with HIV: those patients who sustain CD4+ lymphocyte levels despite ongoing replication, and two control groups, long-term nonprogressors, and those patients who demonstrate a declining CD4+ count in the face of a rapid rebound In viral load while on Highly Active Antiretroviral Therapy (HAART). Collaboration with the Duke University Center. for AIDS Research (CFAR) will permit integration of basic science capabilities with the clinical research program. In addition, collaboration is being established with virology laboratories in order to determine whether these disconnected CD4+ lymphocyte/virologic responses are due to changes in the pathogenicity of the virus as a result of HAART. In the near term, data from this work will be helpful in shaping HAART guidelines, and assessing the effectiveness of a patient's response to therapy. In the long term, characterization of the immune response to HIV will be important in vaccine development. In addition to the described project, the medical student, Susan A. Sufka, will begin coursework towards a Master of Health Science in Clinical Research through the Duke University Clinical Research Training Program. This will allow her to obtain formalized training in the quantitative and methodological principles of clinical research. The combination of the described research project and the didactic experience of the Clinical Research Training Program will provide an ideal environment for the medical student to gain exposure to patient-oriented clinical research, accomplishing the goals of this program announcement.